Fall In Urine Flow Research Articles

Role of ANG II in mediating somatosensory-induced renal nerve-dependent antinatriuresis in the rat.

This study examined the renal nerve-dependent renal hemodynamic and tubular responses to somatosensory stimulation in the anesthetized rat by use of subcutaneously applied capsaicin when the action of ANG II was blocked peripherally or selectively within the brain. Activation of skin somatosensory receptors caused a transient reversible 10-15% increase in blood pressure, and while renal perfusion pressure was regulated at control levels, there was a transient fall in urine flow and sodium excretion even though both renal blood flow and glomerular filtration rate were unchanged. These reflexly induced excretory responses were abolished when the renal nerves were sectioned. Administration of the ANG II AT1-receptor antagonist, losartan, either intravenously at 3 or 10 mg/kg or locally into the lateral cerebroventricles at 15 microg plus 7.5 microg/h, had no effect on capsaicin-induced vasopressor responses but blocked the reductions in urine flow and sodium excretion. These findings are consistent with ANG II being involved in at least two stages in the reflex, one centrally and one at the periphery.

Influence of fluid resuscitation on renal function in bacteremic and endotoxemic rats

Purpose: Fluid resuscitation, which is the most important primary therapy in sepsis, is not always able to prevent acute renal failure. In this study, we investigated in two different rat models of distributive shock whether fluid resuscitation would increase renal plasma flow (RPF) and subsequently glomerular filtration rate (GFR). Materials and Methods: In pentobarbital anesthetized Wistar rats Haemaccel (Behring Pharma, Hoechst, the Netherlands) infusion (1.2 mL/100 g/h for 3 hours) was started immediately during either bacteremia (bolus of living Escherichia coli bacteria, 109 or endotoxemia (1 hour infusion of E. coli endotoxin, 8 mg/kg), as well as in time-matched healthy controls. Results: After 3 hours, this treatment had increased RPF (clearance of 1311-hippurate) above normal in control (+67%) and bacteremic rats (+75%), whereas in endotoxemic animals, the significantly decreased RPF was normalized. On the other hand, in bacteremic animals, the lowered GFR (clearance of creatinine; ×44%) was normalized, whereas in endotoxemic animals GFR remained depressed (×30%). The lack of improvement in GFR during endotoxemia was also indicated by a profound fall in urine flow, which by contrast steadily increased in control and bacteremic rats owing to volume loading. In both shocked groups, the decreased renal oxygen delivery was normalized, but the higher renal oxygen consumption than expected on the basis of the work needed for sodium reabsorption was not influenced by Haemaccel treatment, despite the fact that it caused this work load to rise in bacteremic but not in endotoxemic rats. In both shock models, renal cortical adenosine triphosphate content did not differ from healthy controls and was not influenced by volume loading. Conclusions: In conclusion, our study suggests that a decrease in GFR caused by live bacteria in the circulation may benefit from fluid resuscitation, while during endotoxemia this therapy could not prevent acute renal failure.

Temporal relationships among fetal urine flow, ANF, and AVP responses to hypertonic infusions

The fetal urine flow response to acute increases in osmolality may be mediated by changes in the plasma concentrations of atrial natriuretic factor (ANF), arginine vasopressin (AVP), and/or angiotensin II (ANG II). To explore this, hypertonic NaCl or mannitol was infused intravascularly over 10 min into chronically catheterized fetal sheep and their mothers simultaneously, followed by a 2-h maternal infusion at 1-2 ml/min to maintain the elevated osmolality. Fetal osmolality rose by 16 mosmol/kgH2O during 13% mannitol and 2.5% NaCl infusions and by 57 mosmol/kgH2O during 7% NaCl infusions. Large increases in fetal urine flow occurred in the three groups with peak flows (average of 304%, P less than 10(-6)) at 0-4 min after the end of the infusion. Flow declined to preinfusion values in all groups at 30-40 min. These changes in urine flow occurred in parallel with a rise (to 223%, P less than 10(-6)) and fall in plasma ANF concentrations. One hour after the infusions, urine flow declined to 50% of control concomitant with elevations in plasma AVP (to 414%, P less than 10(-6)), whereas plasma ANG II concentration did not change. Thus the initial increase in fetal urine flow in response to acute hypertonic infusions is temporally related to a rise in fetal plasma ANF, whereas the subsequent fall in urine flow is temporally related to a fall in plasma ANF and a simultaneous rise in AVP concentration. This suggests that ANF may contribute to the acute urine flow increase after hypertonic infusion, whereas AVP appears to be more important for the long-term regulation of fetal urine flow.

Renal response to vasopressin and indomethacin in cisplatin-treated rats.

1. Cisplatin [6 mg/kg body weight, in 0.9% (w/v) NaCl] was injected intraperitoneally as a single dose to two groups of rats (Fischer 344 strain). Two further groups of rats, injected intraperitoneally with an equivalent volume of 0.9% (w/v) NaCl, were used as controls. The cisplatin-treated rats developed a pronounced polyuria which did not recover during an 18 week observation period. 2. After 21 weeks, one group of the cisplatin-treated animals received a 6 h infusion of 2.5% D-glucose. Vasopressin (60 mu-units min-1 100 g-1 body weight) was incorporated into the infusate for the final 2 h. A control group of animals received an identical infusion. One week later the other group of cisplatin-treated rats received a 6 h infusion of 0.9% (w/v) NaCl. Indomethacin was incorporated into the infusate for 15 min, at 3 h 52.5 min, to deliver a dose of 10 mg/kg body weight. A control group again received an identical infusion. 3. Cisplatin did not impair the antidiuretic effect of vasopressin, but it reduced the natriuretic effect of vasopressin, and also impaired the ability of the animals to produce concentrated urine. 4. Cisplatin did not alter basal PGE2 excretion, or the reduction in PGE2 excretion induced by indomethacin. However, the urine flow in the cisplatin-treated group did not fall after indomethacin, whereas there was a fall in urine flow in the control group.

Renal effects of gastrin C-terminal tetrapeptide (as pentagastrin) and cholecystokinin octapeptide in conscious rabbit and man.

Pentagastrin and cholecystokinin octapeptide (CCK8) were infused i.v. at three different doses in two sets of 4 conscious rabbits following a repeated measurements design (130, 1,300 and 13,000 pmol kg-1 min-1 pentagastrin; 5, 50 and 450 pmol kg-1 min-1 CCK8). In man, two different doses of pentagastrin (13 and 65 pmol kg-1 min-1) were infused in two groups of 6 subjects, and CCK8 (2 pmol kg-1 min-1) in a third group. According to published human postprandial levels, plasma CCK8-like immunoreactivity concentrations were supraphysiological at all doses infused. In the rabbit, pentagastrin produced a dose-related fall in urine flow and free water clearance, but no significant change in systemic and renal haemodynamics, electrolyte excretion and measured plasma constituents; however, in human subjects, pentagastrin increased renal sodium excretion and reduced potassium excretion but did not change glomerular filtration rate. In the rabbit, CCK8 produced a dose-related fall in plasma renin activity, plasma calcium concentration and mean arterial blood pressure; dose-dependent increases in effective renal plasma flow, glomerular filtration rate and renal sodium excretion. In man, changes in sodium and potassium excretion similar to pentagastrin were observed; there were no significant changes in plasma renin activity, plasma calcium concentration, blood pressure, effective renal plasma flow or glomerular filtration rate. The pharmacological renal effects of pentagastrin in conscious water-loaded rabbits resemble vasopressin. In contrast, CCK8's most striking effect was vasodilatation and was unusual in inhibiting rather than stimulating renin release. In man the net changes in urine composition found during infusion of these peptides are similar to those produced by the potassium-sparing diuretics, amiloride and triamterene. However the generally weak renal effects observed, even at pharmacological doses, indicate that these peptides are unlikely to influence renal function under normal physiological conditions.

Central effects of dopamine on vasopressin release in the normally hydrated and water-loaded rat.

The effect of intracerebroventricular (I.C.V.) micro-injections of dopamine on vasopressin (AVP) release was investigated in normally hydrated and hydrated rats anaesthetized with urethane, hormone concentrations being determined by radioimmunoassay. Dopamine given in doses of less than 25 micrograms had little effect on AVP concentrations already elevated as a result of anaesthesia and surgery. Doses of over 25 micrograms produced a transient increase in AVP concentrations followed by a fall. Both the increase and the fall were statistically significant. Pimozide (400 micrograms/kg) blocked the fall in AVP concentrations following dopamine. A fall was still seen after the administration of haloperidol (400 micrograms/kg) but it was only significant 20 min after the injection of dopamine. The changes in AVP concentration after the administration of naloxone (400 micrograms/kg) were not statistically significant. In water-loaded rats I.C.V. micro-injections of dopamine produced a dose-dependent antidiuresis over the range 1-25 micrograms. An injection of 25 micrograms dopamine in these animals produced an increase in AVP concentrations to 1.8 +/- 0.51 microunits/ml and a fall in urine flow which could be approximately matched by an infusion of vasopressin of 15 microunits/min. The antidiuresis in response to dopamine could be blocked by haloperidol. The response to dopamine in the anaesthetized animals depends on a number of factors including the initial activity of the neurohypophysial system.

The effect of prostaglandin synthetase inhibitors on renal function: Studies in normal rats during sodium or water diuresis and in rats with chronic renal insufficiency

The effect of acute infusion of the prostaglandin synthetase inhibitors — meclofenamate or indomethacin — was examined in awake rats. Studies were performed in normal rats undergoing either sodium or water diuresis and in salt-replete rats with chronic renal insufficiency. Prostaglandin synthetase inhibitors had no effect on renal plasma flow, glomerular filtration rate or fractional excretion of sodium in any of the groups. Absolute urinary excretion rates for sodium and potassium decreased only in the normal, salt-replete rats. In contrast, prostaglandin synthetase inhibitors consistently decreased urinary flow and osmolar clearance under all experimental conditions studied. In the normal, salt-replete rats the fall in urine flow was preceded by an increase in urinary excretion of cyclic AMP. These results show that inhibitors of prostaglandin synthesis enhance the ability of the kidney to reabsorb water. This effect may be secondary to increased cyclic AMP generation and to increased urea recirculation resulting in higher urea accumulation in the renal medulla.

Renal effects of cyclic AMP in normal and congenital diabetes insipidus rats

The administration of dibutyryl cyclic AMP to normal rats undergoing water diuresis and to rats with congenital diabetes insipidus resulted in a rise in the excretion of Na + and K +. A reduction in free water clearance was also observed in the normal rat, but this could not be entirely attributed to the effect of the nucleotide alone. Infusion of cyclic AMP to Brattleboro rats led to a modest rise in urine osmolality and a fall in urine flow, free water clearance and solute excretion, all of which could be explained on the basis of a fall in GFR. From the present experiments, it may be concluded that at the doses used neither cyclic AMP nor its dibutyryl derivative mimic the effects of ADH on water reabsorption by the kidney in vivo.

The role of a renal thirst factor in drinking induced by extracellular stimuli.

1. Rats in normal fluid balance drank water 1-2 hr after complete ligation of the inferior vena cava either above or below the renal veins. At the same time there was a fall in urine flow and excretion of electrolyte, especially after caval ligation above the renal veins, so that the animals ended the initial 6 hr period in positive fluid balance.2. Caval ligation was relatively ineffective as a stimulus to drinking after bilateral nephrectomy, but was effective in rats made anuric by ureteric ligation.3. Rats subjected to caval ligation and offered a choice between water and 1.8% saline (w/v) drank water, despite the increasing hypotonicity of the body fluids thereby resulting.4. During the secondary polydipsia, which generally occurred on about the third day after caval ligation as renal function was recovering, there was an increased preference for 1.8% saline.5. Constriction of the aorta above the renal arteries, or constriction of both renal arteries, also caused drinking, oliguria and the development of positive fluid balance.6. Constriction of the aorta below the renal arteries, or after nephrectomy, was ineffective as a stimulus to drinking.7. Saline extracts of renal cortex caused rats in normal water balance to drink. Activity was destroyed by boiling the extract for 10 min. Renal medullary and hepatic extracts were without effect on drinking.8. It proved impossible to separate dipsogenic and pressor activities of renal extracts during the different stages of fractionation which lead to the production of renin; disappearance of one activity was invariably accompanied by disappearance of the other.9. Dipsogenic and pressor actions were greater in nephrectomized rats than in normal rats.10. Both extractable dipsogenic factor and extractable pressor activity were reduced by treating the rat with DOCA and saline for several weeks beforehand.11. The renal dipsogen therefore has similar properties to renin. It may prove to be identical with renin, particularly in view of the fact that angiotensin also stimulates drinking.12. Adrenalectomy did not affect drinking induced by renin or by caval ligation.13. It is concluded that the renin angiotensin system may play a role in the genesis of the thirst which follows certain extracellular stimuli.

The value of rats with hereditary hypothalamic diabetes insipidus for the bioassay of vasopressin.

SUMMARY The pituitary glands of 11 rats (six females and five males, weighing 140–200g.) with hereditary hypothalamic diabetes insipidus (DI) were found to contain oxytocin but no vasopressin. The DI rats could not always be distinguished from rats without diabetes insipidus (non-diabetes insipidus, NDI rats) by measurement of their daily urine volume. Stimulation of the neurohypophysis by fall in arterial pressure (haemorrhage, methacholine) or by nicotine, released vasopressin in NDI rats to produce a sustained antidiuresis, but in the DI rats there was only a transient fall in urine flow which did not outlast the hypotension. The DI rats were about twice as sensitive to vasopressin as NDI rats. As assay preparations they have the advantage that they cannot respond to vasopressin-releasing stimuli. Prolonged administration of Pitressin tannate in oil increased maximum urinary osmolality in DI rats, but failed to increase their sensitivity to intravenously injected vasopressin.

The role of aldosterone and vasopressin in the postural changes in renal excretion in normal subjects and patients with idiopathic edema

The effects of the upright posture (leisurely walking for 2 hours) on half-hourly urine volume, and excretion of sodium and creatinine were studied in 13 normal subjects, and 13 patients with idiopathic edema, while they drank 150 or 300 ml. of 0.14 per cent sodium chloride solution every half hour. When the 2 hours of walking were compared with a preceding recumbent period of 4 hours, both groups were found to show a significant antidiuresis upright. The administration of ethanol during the last half hour of recumbency abolished the fall in urine flow and in free water clearance during the first hour of walking in the normal subjects and significantly reduced this fall in the patients with edema. Sodium excretion in the normal subjects was slightly but not significantly lower when upright than when recumbent, but in the edematous patients was significantly lower when upright and fell progressively over the 2 hour period. Administration of spironolactone or D-amphetamine increased sodium excretion during recumbency in both groups but increased sodium excretion upright only in the edematous patients to equal that of the normal subjects. Creatinine excretion was not changed in either group by posture or drug therapy. Similar studies were performed on 5 patients with untreated diabetes insipidus and on 6 patients with adrenal insufficiency treated with hydrocortisone alone. Lack of aldosterone (in adrenal insufficiency) did not increase the amount of sodium excreted above that of normal subjects in recumbency and did not prevent the occurrence of significant sodium retention in the upright posture. However, lack of ADH (in diabetes insipidus) delayed the antidiuresis upright for 30 minutes. The results indicate that ADH release is probably responsible for the reduction in urine volume during the first 30 minutes after assuming the upright posture, but not thereafter. The excessive magnitude of the orthostatic antidiuresis in idiopathic edema probably results from a cause other than ADH release, since it is not completely overcome by ethanol. Reduced Na excretion during 2 hours in the upright posture can occur in the absence of circulating aldosterone, but the abnormal magnitude of the Na retention in the patients with idiopathic edema probably results from hyperal-dosteronism.

Studies on the antidiuretic action of aminopyrine

Changes in urine flow, urine osmolality, and endogenous creatinine clearance were measured after the administration of aminopyrine to water-loaded, anesthetized dogs. A minimum dose of 200 mg./Kg. of aminopyrine was required to produce an antidiuresis with production of a hypertonic urine, when given intravenously. A dose of 2.5 mg./Kg. into the carotid artery was sufficient to produce a profound fall in urine flow and rise in urine osmolality. Some fall in creatinine clearance accompanied the antidiuresis produced by intravenous aminopyrine, but not intracarotid aminopyrine. It is concluded that aminopyrine acts directly on the hypothalamicopituitary axis to increase ADH activity.

Response of isolated perfused dog kidneys to epinephrine

To investigate the renal vascular changes induced by epinephrine, 21 isolated dog kidneys were perfused at constant pressure. Single injections and constant infusions of epinephrine were administered. Changes in blood and urine flow and arterial and intrarenal venous pressures were measured. Changes in renal volume were estimated with a kidney-weighing device, and determinations of cation concentrations were carried out. Data do not support the view that low doses of epinephrine cause diuresis. The previously reported afferent dilation and efferent constriction after epinephrine administration were not found in this investigation. Both increased and decreased urine flows were noted at low doses of epinephrine, whereas a fall in urine flow was consistently seen at high doses. The primary vascular effect of epinephrine is presumably on the afferent arteriole, since there was no consistent diuresis, no increase in kidney weight, a decrease in blood flow, and a decrease in filtration. Electrolyte excretion was not directly influenced by epinephrine. The pressure in the ureter was changed by epinephrine.

Renal function in human pregnancy. V. Effects of oxytocin on renal hemodynamics and water and electrolyte excretion.

Abstract It is generally believed that oxytocin exerts a minimal antidiuretic effect when compared to Pitressin or that it may, in certain animal species, exert a diuretic action. In this study, the effects of oxytocin on renal hemodynamics and water and electrolyte excretion were studied in pregnant and nonpregnant women, in healthy men, and in patients with diabetes insipidus. One natural and two synthetic oxytocic preparations were employed. In each instance, the intravenous infusion of oxytocin induced a marked fall in urine flow which lasted for the duration of the infusion. Renal plasma flow, glomerular filtration rate, electrolyte excretion, and osmolal clearance did not change significantly, whereas free water clearance fell, and often became negative. In the pregnant subjects who received oxytocin for labor induction, the antidiuretic action became evident before the oxytocic effect. Rapid intravenous injections of single doses of oxytocin did not have any action on the urine flow. To investigate the possibility that oxytocin antidiuresis might be mediated through stimulation of antidiuretic hormone secretion, oxytocin was infused, into two patients with diabetes insipidus and three normal subjects whose endogenous antidiuretic hormone release had been blocked by alcohol. The same fall in urine flow and in the free water clearance occurred, suggesting that oxytocin has a direct action on the kidney. It is concluded that in man oxytocin has antidiuretic properties closely similar to those of Pitressin.

Renal function in human pregnancy. III. Effects of antidiuretic hormone (ADH) on renal hemodynamics and water and electrolyte excretion near term and post partum.

It has been suggested that pregnant women are less sensitive to the action of ADH because they possess an inactivating mechanism for this hormone. This hypothesis was tested by studying the effects of intravenous administration of Pitressin on renal hemodynamics and water and electrolyte excretion in pregnant women in the latter part of gestation and in postpartum and nonpregnant subjects. During pregnancy, a single intravenous dose of 100 milliunits (m.u.) of Pitressin or continuous infusion of this hormone in doses varying from 25 to 100 m.u. per hour produced a marked fall in urine flow with a simultaneous fall in renal plasma flow, glomerular filtration rate, and the output of sodium, chloride and total solute. Potassium excretion was inconsistent. Osmolal and free water clearances fell, the latter becoming negative in most instances. Following delivery or in the nonpregnant state, the same or higher doses of Pitressin produced a reduction in urine flow which was of the same magnitude and pattern as that in the pregnant subjects. However, renal hemodynamics remained unchanged and electrolyte excretion even increased. This response was typical of the action of Pitressin as described in the literature. Although various hypotheses are offered to explain the altered response to Pitressin in pregnancy, at present it is not possible to identify precisely the factors that account for the change in renal hemodynamics and the fall in solute excretion. The results of the present study do not lend support to the hypothesis suggested by others that an inactivating mechanism for ADH exists in human pregnancy.

The role of body fluid volume and plasma active osmotic pressure in the control of urine flow and fluid intake in man.

SummaryObservations of body weight, plasma osmotic pressure, daily urine flow and daily fluid intake in a patient recovering from an œdematous state indicate that changes in both plasma osmotic pressure and body fluid volume have an influence on the volume of urine formed, and possibly on the volume of fluid drunk.The control system acts in such a way that a rise of plasma osmotic pressure produces a fall in urine flow and a rise in body fluid volume produces an increase in urine flow.A method is described which enables plasma freezing point to be determined on one millilitre of plasma.